2j25



PARTIALLY DEGLYCOSYLATED GLUCOCERAMIDASE

(see also Treatment of Gaucher disease)

 The structural alignment of the crystal structure of velaglucerase alfa (colored red) (2wkl) reveals that it is very similar to those of the recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase, Cerezyme®, colored blueviolet, 2j25) and in transgenic carrot cells (prGCD, 2v3f). Superposition of the two individual molecules in the asymmetric unit of velaglucerase alfa and imiglucerase demonstrates striking similarity between positions of catalytic residues E235 and E340 (colored orange) in all 4 molecules. The position of H311 is also very similar in all 4 molecules, whereas the conformations of 3 other active site residues W312, Y313, and, especially N396 are somewhat different. The active site residues (except E235 and E340 ) of the two individual molecules in the asymmetric unit of velaglucerase alfa are colored: subunit A (red), subunit B (lime) and of imiglucerase: subunit A (blueviolet) , subunit B (magenta). Imiglucerase and pr-GlcCerase contain a histidine at residue 495 (blueviolet), whereas velaglucerase alfa contains arginine (red). Mutations which cause Gaucher disease, R496 and D474 are close to R495 near the N-terminus of GlcCerase. The <scene name='2wkl/Al/11'>velaglucerase alfa (<font color='blue'>its glycans are colored blue ) and <scene name='2wkl/Al/12'>imiglucerase (<font color='magenta'>its glycans are colored magenta ) have different carbohydrate composition.

About this Structure
2J25 is a [Single protein] structure of acid-beta-glucosidase from [Homo sapiens] with NAG and SO4 as [ligands]. Active as [Glucosylceramidase], with EC number [3.2.1.45]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

Reference
Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease., Brumshtein B, Wormald MR, Silman I, Futerman AH, Sussman JL, Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1458-65. Epub 2006, Nov 23. PMID:17139081

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